Neuropathic pain is a global medical concern, characterized by spontaneous pain, heat hyperalgesia and mechanical allodynia. The condition has been associated with alterations in the voltage‑gated sodium channels, Nav1.8 and Nav1.9, in nociceptive neurons termed nociceptors. However, an explanation for the contribution of these channels to the phenotype observed in neuropathic pain remains to be elucidated. The changes induced by chronic constriction injury (CCI) to Nav1.8 and Nav1.9 mRNA and protein levels, as well as electrical currents in injured and contralateral non‑injured dorsal root ganglion (DRG) neurons are described in the present study. A marked downregulation was observed for each Nav isoform transcript and protein expressed in injured neurons with the exception of the Nav1.9 protein, which exhibited no change, while in contralateral non‑injured neurons, the levels of protein and mRNA remained unchanged. Nav isoform functional analysis was then performed in L(4‑6) DRG neurons 14 days after CCI. The Nav1.8 current density was markedly decreased in injured DRG neurons following CCI. The voltage‑dependent activation of the Nav1.8 channel in these neurons was shifted to depolarized potentials by 5.3 mV, while it was shifted to hyperpolarized potentials by 10 mV for inactivation. The electrophysiological function of Nav1.9 was not affected by CCI. The present study demonstrated that ectopic discharge following CCI, which was likely induced by a positive shift in the Nav1.8 current inactivation curve in injured neurons, enhanced the excitability of the neurons by facilitating tetrodotoxin‑resistant sodium channels into the fast inactivation state and did not occur as a result of a compensatory redistribution in the contralateral uninjured neurons.

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The analgesic studies on Stauntonia brachyanthera, a traditional Chinese folk medicine used to treat headache, pains and inflammatory diseases in local areas, showed that the EtOH extracts (EESB) and the characteristic ingredient YM11 could significantly inhibit the acetic acid-induced writhing responses by 43.1% and 78.95%, and decrease the xylene-induced ear edemas by 48.9% and 21.4%, respectively. EESB could significantly increase pain threshold of mice in hot-plate test, but the effect of YM11 was not obviously. Further study in formalin test showed the inhibitory effect of YM11 in 2nd phase was more significant than that in 1st phase, revealed the peripheral analgesic activity of YM11. The ELISA and Western Blot analysis suggested that the analgesic mechanisms of YM11 were related to the inhibitions of the expressions of TNF-α, IL-1β and IL-6, and down-regulations of Nav1.8 protein in the left side of L4–6 DRG regulated by MAPKs, in which the levels of p-ERK, p-JNK and p-p38 were all decreased. In addition, the electrophysiological experiments indicated YM11 could reduce the Nav1.8 currents by 46.01% in small-diameter DRG neurons. Therefore, the analgesic activity of S. brachyanthera might be based on the regulation of inflammatory mediators and the directly control of the sodium channel prompt.